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Defining and understanding ‘asthma mimicks’

Reviewed By Allergy, Immunology & Inflammation Assembly

Submitted by

Daniel J. Schneider MD, PhD

Clinical Lecturer

Department of Internal Medicine

University of Michigan Hospitals

Ann Arbor, MI

Submit your comments to the author(s).


Learning objectives:

  • Review the differential diagnosis for severe asthma with eosinophilia and pulmonary infiltrates.
  • Understand the historical, laboratory, imaging, and histopathologic manifestations of conditions that ‘mimick’ severe asthma.
  • Explore novel biologic treatment options for management of eosinophilia.

22 year old male with a history of rhinorrhea and nasal congestion as a child presented with shortness of breath and cough. He is a lifelong non-smoker and has no history of respiratory symptoms until 1 year prior to presentation. In the span of the preceding year, he experienced 5 episodes of chest congestion, productive cough, wheezing, and shortness of breath which were treated successfully, albeit temporarily with varying doses of prednisone. He lives in Michigan and has not traveled outside of the state recently. At this time he was also diagnosed with nasal polyps. Initial maintenance treatments for his asthma included budesonide/formoterol 160/4.5 mcg twice daily, montelukast 10mg daily, prednisone 20mg daily, and cetirizine 10mg daily. Based on an elevated IgE he was eventually started on omalizumab without adequate control of his symptoms.

Pertinent laboratory evaluation performed at the time included myeloperoxidase and proteinase 3 ANCA which were negative, absolute eosinophil count and total IgE were elevated at 4.6k/μL and 512 kU/L, respectively. Bronchoscopy was performed which showed 68% eosinophils on BAL cell differential and no evidence of infection. He was started on benralizumab given his peripheral and airway eosinophilia despite 20mg of prednisone.

Despite this initiation, he developed generalized abdominal pain, nausea, vomiting, diarrhea, fevers at home (38.9 °C), lymphadenopathy, and worsening shortness of breath which lead to a hospital admission. It was noted on interview that he had been unable to refill his prednisone 1 week prior to the admission.

Physical Exam

Pertinent physical exam findings:

Temp: 37.2 °C, BP 148/90, HR: 116, Resp: 20, SPO2: 99% RA

Rales throughout all lung fields, greatest at right base. Abdomen tender to palpation in right upper quadrant.

Outpatient pulmonary function testing:

Oximetry at rest on room air: 94%

  Absolute % Predicted
FVC 4.73 L 80%
FEV1 2.89 L 62%
FEV1:FVC 61% 77%


Laboratory evaluation at admission

Basic metabolic panel normal including Cr 0.83

WBC 14.2 K/μL, Hgb 13.2 g/dL, Plt 479 K/μL, Abs eos 0.4 K/μL

ESR 68, CRP 9.8 (0.0 - 0.6), ANA negative, repeat ANCA negative

IgE 4763 kU/L,  Aspergillus IgE < 0.35 kU/L




Protein Negative
Color Yellow


Glucose Negative
Appearance Normal


Ketones Negative
Specific Gravity 1.022


Urobilinogen Negative
pH 7.0


Bilirubin Negative
Leukocyte esterase Negative


Blood Negative
Nitrite Negative RBC/HPF Negative

Stool ova and parasite testing, stool viral PCR panel, and strongyloides antibody were all negative.

Imaging performed during admission

CT scan of the abdomen and pelvis:  notable for wall thickening and mucosal enhancement of the duodenum and proximal jejunum consistent with enteritis that could be infectious or inflammatory in nature.  Small amount of surrounding free fluid. 

High resolution CT of the chest: (representative image shown; inspiratory (left) expiratory (right))

image 1

image 2

Transthoracic echocardiogram: Normal LV/RV function.

Procedures and associated histology findings during admission:

Endoscopy and push enteroscopy: gastric, duodenal, and jejunal biopsies were taken. All biopsies were negative for eosinophilic infiltrates or viral inclusions.

Repeat bronchoscopy: showed a decline in airway eosinophils to 2% and BAL cultures were again negative. Transbronchial biopsies showed only normal and exfoliated respiratory epithelium. Notably, the patient had 1 dose of prednisone 20mg the day prior to repeat bronchoscopy.

Bone marrow biopsy: normocellular aspirate, trilineage hematopoiesis, and peripheral eosinophilia consistent with reactive eosinophilia. (serum absolute eosinophils 3.9 K/μL at time of biopsy)

Flow cytometry was normal

Fluorescent in situ hybridization and showed a normal male karyotype;

notable absence of FIP1L1/PDGFRA gene fusion, rearrangements, or mutations within of PDGFRA, PDGFRB, FGFR1 or JAK2 genes.

Clonal rearrangement in T cell receptor β (TRB) was detected

Video-assisted thorascopic surgery wedge biopsy of the right lower lobe: – H&E sections (3):

image 3
image 4

Question 1

What is/are the most likely diagnosis?


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